Both BCG and dehydroepiandrosterone (DHEA) induce Th1 immune responses and suppress Th2 allergic reactions. To investigate whether the combination of BCG and DHEA has an additive effect on asthma prevention, BALB/c mice (n = 10 per group) were given an intraperitoneal injection of BCG at the beginning of sensitization, and fed mice chow containing DHEA throughout the study. In female mice, the combined administration of 2 x 10(4) CFUs BCG and 0.01% DHEA effectively suppressed the ovalbumin-induced increase in airway sensitivity to methacholine (56.5 vs. 8.2 mg/mL, p < 0.01), while BCG (13.9 mg/mL) or DHEA (17.9 mg/mL) alone did not. However, the addition of high dose (0.1%) DHEA decreased the efficacy of high dose (2 x 10(5) CFUs) BCG in suppressing the airway responsiveness and eosinophilia. In male mice, the treatments with BCG and/or DHEA were less effective, and the interferon-gamma / interleukin-4 ratio in the splenocyte supernatant was significantly higher and the ovalbumin-specific IgE concentration in the serum was significantly lower as compared to female mice. In conclusion, the combination of low doses of BCG and DHEA had an additive effect in suppressing the development of airway hypersensitivity. Androgens in males and DHEA overdose might reduce the efficacy of BCG.